Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 223 (16 Oct 2019)
Sequence version 1 (01 Nov 1995)
Previous versions | rss
Help videoAdd a publicationFeedback
Protein

DNA mismatch repair protein Msh2

Gene

MSH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containg DNA strand (PubMed:26300262). ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.9 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi669 – 676ATPSequence analysis8

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA repair
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5632927 Defective Mismatch Repair Associated With MSH3
R-HSA-5632928 Defective Mismatch Repair Associated With MSH2
R-HSA-5632968 Defective Mismatch Repair Associated With MSH6
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes

SIGNOR Signaling Network Open Resource

More...
SIGNORi
P43246

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
DNA mismatch repair protein Msh2
Short name:
hMSH2
Alternative name(s):
MutS protein homolog 2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MSH2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 2

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:7325 MSH2

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
609309 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P43246

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Hereditary non-polyposis colorectal cancer 1 (HNPCC1)54 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_0545112A → T in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750466EnsemblClinVar.1
Natural variantiVAR_04373833T → P in HNPCC1; decreased mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63751107EnsemblClinVar.1
Natural variantiVAR_04374044T → M in HNPCC1; unknown pathological significance; no decrease in mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs587779085EnsemblClinVar.1
Natural variantiVAR_04374145A → V in HNPCC1; unknown pathological significance; no decrease in mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750285EnsemblClinVar.1
Natural variantiVAR_00447046H → Q in HNPCC1. 2 PublicationsCorresponds to variant dbSNP:rs33946261EnsemblClinVar.1
Natural variantiVAR_04374292Missing in HNPCC1; unknown pathological significance. 3 Publications1
Natural variantiVAR_04374393L → F in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751429EnsemblClinVar.1
Natural variantiVAR_04374498Y → C in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750887EnsemblClinVar.1
Natural variantiVAR_043745102V → I in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs193922373EnsemblClinVar.1
Natural variantiVAR_043746110K → T in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_019234127N → S in HNPCC1; presumed to enhance cancer risk considerably when associated with P-328; shows significantly decreased repair efficiency when associated with variant P-328. 5 PublicationsCorresponds to variant dbSNP:rs17217772EnsemblClinVar.1
Natural variantiVAR_004472139N → S in HNPCC1. Corresponds to variant dbSNP:rs1553350676EnsemblClinVar.1
Natural variantiVAR_004473145I → M in HNPCC1; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750124EnsemblClinVar.1
Natural variantiVAR_012936161V → D in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 4 PublicationsCorresponds to variant dbSNP:rs63750126EnsemblClinVar.1
Natural variantiVAR_054512162G → A in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750773EnsemblClinVar.1
Natural variantiVAR_043747162G → R in HNPCC1; decreased mismatch repair activity; associated with an abnormal subcellular localization pattern; affects protein stability; loss of protein expression. 5 PublicationsCorresponds to variant dbSNP:rs63750624EnsemblClinVar.1
Natural variantiVAR_043748163V → D in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750214EnsemblClinVar.1
Natural variantiVAR_022670163V → G in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750214EnsemblClinVar.1
Natural variantiVAR_043749164G → R in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63750582EnsemblClinVar.1
Natural variantiVAR_067284165Y → D in HNPCC1; unknown pathological significance; decreased mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779163EnsemblClinVar.1
Natural variantiVAR_004474167D → H in HNPCC1; shows reduced mismatch binding; does not show a decreased expression level of the MutS alpha complex; not associated with an abnormal subcellular localization pattern; normal mismatch repair activity. 6 PublicationsCorresponds to variant dbSNP:rs63750255EnsemblClinVar.1
Natural variantiVAR_043750169I → V in HNPCC1 and CRC; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs63750716EnsemblClinVar.1
Natural variantiVAR_043751173L → P in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63750070EnsemblClinVar.1
Natural variantiVAR_043752175L → P in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751291EnsemblClinVar.1
Natural variantiVAR_067285177E → H in HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_043753187L → P in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63751444EnsemblClinVar.1
Natural variantiVAR_076352187L → R in HNPCC1; decreased mismatch repair activity; loss of protein expression. 1 PublicationCorresponds to variant dbSNP:rs63751444EnsemblClinVar.1
Natural variantiVAR_054513198E → G in HNPCC1. Corresponds to variant dbSNP:rs63750327EnsemblClinVar.1
Natural variantiVAR_012938216I → V in HNPCC1; unknown pathological significance; shows slightly reduced mismatch binding or release efficiency. 1 PublicationCorresponds to variant dbSNP:rs63749936EnsemblClinVar.1
Natural variantiVAR_043755246K → Q in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750881EnsemblClinVar.1
Natural variantiVAR_004475265 – 314Missing in HNPCC1. 1 PublicationAdd BLAST50
Natural variantiVAR_043756272A → V in HNPCC1; unknown pathological significance; shows slightly reduced mismatch binding or release efficiency; results in partial MSH2 exon 5 skipping; normal mismatch repair activity. 5 PublicationsCorresponds to variant dbSNP:rs34136999EnsemblClinVar.1
Natural variantiVAR_043757283D → Y in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750381EnsemblClinVar.1
Natural variantiVAR_004476305A → T in HNPCC1; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63751454EnsemblClinVar.1
Natural variantiVAR_012939323S → C in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750732EnsemblClinVar.1
Natural variantiVAR_043758323S → Y in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750732EnsemblClinVar.1
Natural variantiVAR_054514331N → D in HNPCC1; no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267607938EnsemblClinVar.1
Natural variantiVAR_043759333C → Y in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63750828EnsemblClinVar.1
Natural variantiVAR_043760335T → I in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750602EnsemblClinVar.1
Natural variantiVAR_043761336P → S in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751062EnsemblClinVar.1
Natural variantiVAR_043763349P → L in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs587779067EnsemblClinVar.1
Natural variantiVAR_043764359R → S in HNPCC1; shows a decreased expression level of the MutS alpha complex; associated with an abnormal subcellular localization pattern. 2 PublicationsCorresponds to variant dbSNP:rs63751617EnsemblClinVar.1
Natural variantiVAR_067286385P → L in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs564736113EnsemblClinVar.1
Natural variantiVAR_004478390L → F in HNPCC1 and CRC; unknown pathological significance; may decrease mismatch repair activity. 9 PublicationsCorresponds to variant dbSNP:rs17224367EnsemblClinVar.1
Natural variantiVAR_043765393K → M in HNPCC1. 1 Publication1
Natural variantiVAR_043766440Missing in HNPCC1. 1 Publication1
Natural variantiVAR_054515470V → E in HNPCC1; has no effect on ex vivo splicing assay. 1 PublicationCorresponds to variant dbSNP:rs267607959EnsemblClinVar.1
Natural variantiVAR_043767492M → V in HNPCC1. 1
Natural variantiVAR_012941506D → Y in HNPCC1 and CRC; sporadic early-onset CRC; decreased mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs63750492EnsemblClinVar.1
Natural variantiVAR_067287519F → L in HNPCC1; unknown pathological significance; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs1371291280Ensembl.1
Natural variantiVAR_004479524R → P in HNPCC1; decreased mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63751207EnsemblClinVar.1
Natural variantiVAR_043768552T → P in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750838EnsemblClinVar.1
Natural variantiVAR_012942554S → R in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751656EnsemblClinVar.1
Natural variantiVAR_004480562E → V in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750997EnsemblClinVar.1
Natural variantiVAR_043769564T → A in HNPCC1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs55778204EnsemblClinVar.1
Natural variantiVAR_043770583N → S in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs201118107EnsemblClinVar.1
Natural variantiVAR_012943596N → S in HNPCC1; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs41295288EnsemblClinVar.1
Natural variantiVAR_004481596Missing in HNPCC1; decreased mismatch repair activity; has no effect on MSH2 splicing. 9 Publications1
Natural variantiVAR_043771600A → V in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751236EnsemblClinVar.1
Natural variantiVAR_043772603D → N in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 4 PublicationsCorresponds to variant dbSNP:rs63750657EnsemblClinVar.1
Natural variantiVAR_054516610H → N in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267607980EnsemblClinVar.1
Natural variantiVAR_004482622P → L in HNPCC1; decreased mismatch repair activity; confers multiple biochemical defects. 5 PublicationsCorresponds to variant dbSNP:rs28929483EnsemblClinVar.1
Natural variantiVAR_043774629Q → R in HNPCC1; unknown pathological significance. 5 PublicationsCorresponds to variant dbSNP:rs61756468EnsemblClinVar.1
Natural variantiVAR_012944636A → P in HNPCC1; decreased mismatch binding activity. 5 PublicationsCorresponds to variant dbSNP:rs63750875EnsemblClinVar.1
Natural variantiVAR_054517638R → G in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267607981EnsemblClinVar.1
Natural variantiVAR_043775639H → R in HNPCC1; decreased mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs587779116EnsemblClinVar.1
Natural variantiVAR_004483639H → Y in HNPCC1; the equivalent substitution in yeast does not affect mismatch repair efficiency in vitro. 2 PublicationsCorresponds to variant dbSNP:rs28929484EnsemblClinVar.1
Natural variantiVAR_054518645Q → E in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267607982EnsemblClinVar.1
Natural variantiVAR_043776647E → K in HNPCC1. 1 Publication1
Natural variantiVAR_043777656Y → H in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_022671660D → G in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs1085308057EnsemblClinVar.1
Natural variantiVAR_067761669G → R in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751668EnsemblClinVar.1
Natural variantiVAR_043778671N → Y in HNPCC1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs63751232EnsemblClinVar.1
Natural variantiVAR_076353674G → A in HNPCC1; decreased mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267607996Ensembl.1
Natural variantiVAR_067288674G → R in HNPCC1; decreased mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750234EnsemblClinVar.1
Natural variantiVAR_004485674G → S in HNPCC1; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs63750234EnsemblClinVar.1
Natural variantiVAR_067289675K → A in HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; decreased mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779128EnsemblClinVar.1
Natural variantiVAR_043779679I → T in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_012945688M → I in HNPCC1. 3 PublicationsCorresponds to variant dbSNP:rs63750790EnsemblClinVar.1
Natural variantiVAR_076354688M → V in HNPCC1; loss of protein expression. 1 Publication1
Natural variantiVAR_009250692G → R in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750232EnsemblClinVar.1
Natural variantiVAR_054519696P → L in HNPCC1; has no effect on ex vivo splicing assay. 1 PublicationCorresponds to variant dbSNP:rs267607994EnsemblClinVar.1
Natural variantiVAR_004486697C → F in HNPCC1; decreased mismatch repair activity; loss of protein expression; confers multiple biochemical defects. 7 PublicationsCorresponds to variant dbSNP:rs63750398EnsemblClinVar.1
Natural variantiVAR_009251697C → R in HNPCC1; has no effect on MSH2 splicing. 2 PublicationsCorresponds to variant dbSNP:rs63750961EnsemblClinVar.1
Natural variantiVAR_043780714A → V in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751224EnsemblClinVar.1
Natural variantiVAR_043781723S → F in HNPCC1; decreased mismatch repair activity; has no effect on MSH2 splicing. 3 PublicationsCorresponds to variant dbSNP:rs63750794EnsemblClinVar.1
Natural variantiVAR_043782729M → V in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_043783732T → I in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_043784745 – 746Missing in HNPCC1; decreased mismatch repair activity. 3 Publications2
Natural variantiVAR_054520748D → Y in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267608007EnsemblClinVar.1
Natural variantiVAR_043785749E → K in HNPCC1; decreased mismatch repair activity; no loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63751477EnsemblClinVar.1
Natural variantiVAR_067290759G → E in HNPCC1; unknown pathological significance; decreased mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs386833406EnsemblClinVar.1
Natural variantiVAR_067291805L → V in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_043786813M → V in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63749841EnsemblClinVar.1
Natural variantiVAR_004488834A → T in HNPCC1; decreased mismatch repair activity; shows no functional defects in gel shift assay. 6 PublicationsCorresponds to variant dbSNP:rs63750757EnsemblClinVar.1
Natural variantiVAR_054521839H → Q in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267608016EnsemblClinVar.1
Natural variantiVAR_043788839H → R in HNPCC1; decreases protein levels. 2 PublicationsCorresponds to variant dbSNP:rs63750027EnsemblClinVar.1
Natural variantiVAR_067292843C → G in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_013172845K → E in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750571EnsemblClinVar.1
Natural variantiVAR_043789853E → A in HNPCC1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs63750797EnsemblClinVar.1
Natural variantiVAR_067293860S → L in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs63750849EnsemblClinVar.1
Natural variantiVAR_043793886E → G in HNPCC1; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750350EnsemblClinVar.1
Natural variantiVAR_004489905T → R in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs267608022EnsemblClinVar.1
Natural variantiVAR_043794923V → E in HNPCC1; unknown pathological significance. 4 PublicationsCorresponds to variant dbSNP:rs146421227EnsemblClinVar.1
Natural variantiVAR_043795931K → T in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs267608023EnsemblClinVar.1
Muir-Torre syndrome (MRTES)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.
Related information in OMIM
Endometrial cancer (ENDMC)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids.
Related information in OMIM
Mismatch repair cancer syndrome (MMRCS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive, rare, childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. Areas of skin hypopigmentation have also been reported in MMRCS patients.
Related information in OMIM
Colorectal cancer (CRC)4 Publications
Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Disease descriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04373613S → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749907EnsemblClinVar.1
Natural variantiVAR_04373940G → S in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751260EnsemblClinVar.1
Natural variantiVAR_043750169I → V in HNPCC1 and CRC; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs63750716EnsemblClinVar.1
Natural variantiVAR_043754203G → R in CRC; unknown pathological significance; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587779973EnsemblClinVar.1
Natural variantiVAR_043762342V → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749879EnsemblClinVar.1
Natural variantiVAR_004478390L → F in HNPCC1 and CRC; unknown pathological significance; may decrease mismatch repair activity. 9 PublicationsCorresponds to variant dbSNP:rs17224367EnsemblClinVar.1
Natural variantiVAR_012940419Q → K in CRC; unknown pathological significance; decreased mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs63750006EnsemblClinVar.1
Natural variantiVAR_012941506D → Y in HNPCC1 and CRC; sporadic early-onset CRC; decreased mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs63750492EnsemblClinVar.1
Natural variantiVAR_043773619Y → C in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749982EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi675K → R: No effect on mismatch binding, complete loss of DNA repair function when associated with MSH6 mutant R-1140. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary nonpolyposis colorectal cancer, Tumor suppressor

Organism-specific databases

DisGeNET

More...
DisGeNETi
4436

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...
GeneReviewsi
MSH2

MalaCards human disease database

More...
MalaCardsi
MSH2
MIMi114500 phenotype
120435 phenotype
158320 phenotype
276300 phenotype
608089 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000095002

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
252202 Constitutional mismatch repair deficiency syndrome
144 Lynch syndrome
587 Muir-Torre syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA31133

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
P43246

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
MSH2

Domain mapping of disease mutations (DMDM)

More...
DMDMi
1171032

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001151832 – 934DNA mismatch repair protein Msh2Add BLAST933

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylalanineCombined sources1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei555N6-acetyllysineCombined sources1
Modified residuei567N6-acetyllysineBy similarity1
Modified residuei921PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
P43246

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
P43246

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...
MassIVEi
P43246

MaxQB - The MaxQuant DataBase

More...
MaxQBi
P43246

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P43246

PeptideAtlas

More...
PeptideAtlasi
P43246

PRoteomics IDEntifications database

More...
PRIDEi
P43246

ProteomicsDB: a multi-organism proteome resource

More...
ProteomicsDBi
55601 [P43246-1]
5866

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P43246

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P43246

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
P43246

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000095002 Expressed in 212 organ(s), highest expression level in secondary oocyte

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P43246 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P43246 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB009572
CAB070867
HPA066845

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta) (PubMed:8942985). Both heterodimers form a ternary complex with MutL alpha (MLH1-PMS1) (PubMed:9788596, PubMed:10856833, PubMed:11427529, PubMed:11429708, PubMed:12414623, PubMed:14676842).

Interacts with MCM9; the interaction recruits MCM9 to chromatin (PubMed:26300262).

Interacts with MCM8 (PubMed:26300262).

Interacts with EXO1 (PubMed:9788596, PubMed:10856833, PubMed:11427529, PubMed:11429708, PubMed:12414623, PubMed:14676842). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10783165).

Interacts with ATR (PubMed:14657349).

Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases (PubMed:19596235).

Interacts with SMARCAD1 (PubMed:18675275).

12 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
110573, 157 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...
ComplexPortali
CPX-77 DNA mismatch repair MutSbeta complex
CPX-80 DNA mismatch repair MutSalpha complex

CORUM comprehensive resource of mammalian protein complexes

More...
CORUMi
P43246

Database of interacting proteins

More...
DIPi
DIP-35054N

Protein interaction database and analysis system

More...
IntActi
P43246, 58 interactors

Molecular INTeraction database

More...
MINTi
P43246

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000233146

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1934
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details